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Background and aimsThis study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy.MethodsIn this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects.Results300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI −4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI −4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI −2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010).ConclusionsVT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT.Trial registration numberChiCTR2300074693.

No study has investigated the efficacy and safety of vonoprazan-amoxicillin dual therapy compared with bismuth quadruple therapy (B-quadruple). This study aimed to evaluate the efficacy and safety of 10-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with B-quadruple and to explore the optimal dosage of amoxicillin in the dual therapy. A total of 375 treatment-naive, H. pylori -infected subjects were randomly assigned in a 1:1:1 ratio into 3 regimen groups including VHA-dual (vonoprazan 20 mg twice/day + amoxicillin 750 mg 4 times/day), VA-dual (vonoprazan 20 mg + amoxicillin 1,000 mg twice/day), and B-quadruple (esomeprazole 20 mg + bismuth 200 mg + amoxicillin 1,000 mg + clarithromycin 500 mg twice/day). Eradication rates, adverse events (AEs), and compliance were compared between 3 groups. The eradication rates of B-quadruple, VHA-dual, and VA-dual were 90.9%, 93.4%, and 85.1%, respectively, by per-protocol analysis; 89.4%, 92.7%, and 84.4%, respectively, by modified intention-to-treat analysis; 88.0%, 91.2%, and 82.4%, respectively, by intention-to-treat analysis. The efficacy of the VHA-dual group was not inferior to the B-quadruple group ( P < 0.001), but VA-dual did not reach a noninferiority margin of -10%. The AEs rates of the B-quadruple group were significantly higher than those of the VHA-dual ( P = 0.012) and VA-dual ( P = 0.001) groups. There was no significant difference in medication compliance among 3 treatment groups ( P = 0.995). The 10-day VHA-dual therapy provided satisfactory eradication rates of >90%, lower AEs rates, and similar adherence compared with B-quadruple therapy as a first-line therapy for H. pylori infection. However, the efficacy of VA-dual therapy was not acceptable.

INTRODUCTION:Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment.METHODS:This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori-infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups.RESULTS:Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% (P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% (P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% (P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group (P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group (P < 0.001), while not in the B-quadruple group (P = 0.110).DISCUSSION:The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy.TRAIL REGISTRATION NUMBER:ChiCTR2300070100.

ObjectiveTo evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy.DesignSubjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial.ResultsTwo hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (eg, susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group.ConclusionsThese results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains.Trial registration numberNCT02175901.

Aim: To establish whether the addition of probiotics to a globally accepted Helicobacter pylori (H. pylori)-eradication scheme may reduce the rates of side effects and increase the eradication rates. Methods. Prospective, randomized, placebo-controlled trial of patients receiving eradication therapy for H. pylori in the eight participating centers. All patients received a 10-day proton pump inhibitor containing non-bismuth quadruple therapeutic regimen for H. pylori eradication (omeprazole 20 mg, amoxycillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg all twice daily orally) and were randomized to receive either probiotics (group A) or placebo (group B). The probiotic used combined four probiotic strains, i.e., Lactobacillus Acidophilus, Lactiplantibacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii. Results. Data were analyzed for 329 patients in group A and 335 patients in group B. Fifty six (17.0%) patients in group A and 170 (50.7%) patients in group B reported the occurrence of an H. pylori treatment-associated new symptom or the aggravation of a pre-existing symptom of any severity (p < 0.00001). H. pylori was successfully eradicated in 303 patients in group A (92.0%) and 291 patients in group B (86.8%), (p = 0.028). Conclusion: Adding probiotics to the 10-day concomitant non-bismuth quadruple H. pylori eradication regimen increases the eradication rate and decreases side effects.

Rifasutenizol (TNP-2198) is a new molecular entity with a synergistic dual mechanism of action under clinical development for the treatment of Helicobacter pylori infection. We aimed to evaluate the efficacy and safety of a rifasutenizol-based triple therapy (RTT) versus bismuth plus clarithromycin-based triple therapy (BCTT) for the treatment of H pylori infection in treatment-naive patients. EVEREST-HP was a phase 3, randomised, triple-dummy, double-blind, active-controlled, non-inferiority trial with adaptive design for sample size re-estimation conducted at 40 research hospitals in China. Treatment-naive patients aged 18–65 years, with a positive [13C]urea breath test ([13C]UBT), further confirmed by gastric biopsy and histological examination, were randomly assigned (1:1) to receive RTT (rifasutenizol 400 mg oral capsules, amoxicillin 1 g oral capsules, and rabeprazole 20 mg enteric-coated tables) or BCTT (bismuth potassium citrate 240 mg oral tablets, clarithromycin 500 mg oral tablets, amoxicillin 1 g oral capsules, and rabeprazole 20 mg enteric-coated tablets), all twice a day for 14 days. Randomisation was done centrally by a secure interactive web response system using block sizes of two or four and stratified by study site. RTT was compared against BCTT using a triple-dummy approach to ensure masking. The primary endpoint was H pylori eradication rate based on [13C]UBT 4–6 weeks after the end of treatment in the modified intention-to-treat population, which included all participants who received at least one dose of the study drugs. The eradication rates of RTT and BCTT were compared using a one-sided α value of 0·025 and a non-inferiority margin of –10%. Safety endpoints included investigator assessed treatment-emergent adverse events, the severity and relationship with study drugs, findings from physical examinations, vital signs, laboratory tests, and electrocardiogram. An interim analysis was conducted by an independent data monitoring committee after 50% (350) of patients completed the last [13C]UBT. The trial is registered with ClinicalTrials.gov, NCT05857163. Between May 18, 2023, and Nov 10, 2023, 1267 patients were screened and 700 patients were randomly assigned to receive either RTT (n=353) or BCTT (n=347). 261 (37%) patients were men and 439 (63%) were women. 351 patients in the RTT group and 346 in the BCTT group took at least one dose of the study drugs and were included in the modified intention-to-treat group and the safety set. H pylori was successfully cultured from 579 (83%) of 697 patients. 236 (41%) of 579 patients had H pylori infection resistant to clarithromycin, 395 (68%) to metronidazole, 203 (35%) to levofloxacin, and 47 (8%) to amoxicillin. All H pylori clinical isolates were susceptible to rifasutenizol. In the modified intention-to-treat analysis, the H pylori eradication rate in the RTT group was non-inferior to that in the BCTT group (92·0% [95% CI 88·7 to 94·6; 323 of 351] vs 87·9% [83·9 to 91·1; 304 of 346]; absolute difference 4·2% [95% CI –0·3 to 8·8]). 131 (37%) of 351 patients in the RTT group and 184 (53%) of 346 in the BCTT group had treatment-emergent adverse events. Treatment-emergent adverse events occurring in more than 5% of patients in the RTT group were diarrhoea (in 24 [7%] patients), nausea (22 [6%]), and dizziness (21 [6%]), and in more than 5% of patients in the BCTT group were taste perversion (125 [36%]), nausea (21 [6%]), and diarrhoea (19 [5%]) Most of the treatment-emergent adverse events were mild or moderate in severity. No serious adverse event related to study drugs was reported. As the first novel antimicrobial agent specifically developed for H pylori infection, rifasutenizol represents a promising addition to the existing options for tackling antimicrobial resistance, and RTT represents a promising first-line treatment option for H pylori infection. TenNor Therapeutics. For the Chinese translation of the abstract see Supplementary Materials section.

Vonoprazan, a novel and potent acid suppressant, has recently been incorporated into Helicobacter pylori eradication regimens. However, the data on combination of vonoprazan with levofloxacin remains scarce. This study represents one of the first evaluations comparing 7-day and 14-day once-daily regimens containing vonoprazan, levofloxacin, clarithromycin-MR, and bismuth for H. pylori eradication in regions characterized by high clarithromycin and metronidazole resistance. Between March 2022 and December 2023, patients presenting with dyspepsia who underwent upper gastrointestinal endoscopy at a tertiary care hospital in Thailand were recruited. Those testing positive for H. pylori infection were randomly assigned to receive either a 7-day or 14-day once-daily regimen comprising vonoprazan 40 mg, clarithromycin-MR 1 g, levofloxacin 500 mg, and bismuth subsalicylate 1,048 mg. CYP3A4 polymorphism testing and antimicrobial susceptibility assessment (using either the Epsilometer test or the GenoType ® HelicoDR assay) were performed. Eradication was confirmed by a negative ¹³C-urea breath test conducted no sooner than four weeks after completing therapy. A total of 312 dyspeptic patients who underwent EGD were screened, and 102 (32.7%) were diagnosed with H. pylori infection. The study enrolled and randomized these patients into two treatment groups: 51 received the 7-day once-daily vonoprazan-based bismuth therapy, and 51 received the 14-day regimen. Baseline characteristics were similar between the two groups, except for a higher prevalence of hypertension in the 7-day regimen group (49% vs. 27.5%, p  = 0.025). The eradication rates for the 7-day regimen were 88.2% (45/51) in the intention-to-treat (ITT) analysis and 89.6% (43/48) in the per-protocol (PP) analysis. Similarly, the 14-day regimen achieved eradication rates of 88.2% (45/51) in the ITT analysis and 93.8% (45/48) in the PP analysis. The risk difference for eradication in the PP analysis was 4.17% (95% CI: -6.86 to 15.19, p  = 0.71). Adverse events were comparable between the two regimens, occurring in 35.3% (18/51) of patients in the 7-day regimen and 38.8% (19/51) in the 14-day regimen ( p  = 0.130). The most frequently reported adverse event was black stool (35.3% vs. 38.8%, p  = 0.130). Other adverse events included nausea and vomiting (15.7% vs. 22.5%, p  = 0.742), bitter taste (17.7% vs. 18.4%, p  = 1.000), and dizziness (7.8% vs. 6.1%, p  = 0.113). All adverse events resolved spontaneously without requiring medical intervention, and no serious adverse events were reported. The 14-day regimen demonstrated excellent eradication rate (> 90%) regardless of CYP3A4 polymorphisms. These findings suggest that vonoprazan, levofloxacin, clarithromycin-MR, and bismuth for 14 days is a promising alternative first-line treatment option, particularly in regions with high clarithromycin and metronidazole resistance.

To compare the efficacy and safety of bismuth-containing quadruple therapy with tetracycline or amoxicillin for rescue treatment of Helicobacter pylori. The study was a non-inferiority trial of H. pylori eradication with at least two previous treatment failures. Subjects were randomized to receive 14-day therapy with b.i.d. lansoprazole 30 mg and bismuth 220 mg, plus metronidazole 400 mg q.i.d and amoxicillin 1 g t.i.d (amoxicillin group) or tetracycline 500 mg q.i.d (tetracycline group). Antimicrobial susceptibility was assessed by the agar-dilution method. Primary outcome was H. pylori eradication at 6 weeks after treatment. In all, 312 subjects were randomized, 13 were lost to follow-up; 29 violated the protocol. The intention-to-treat, per-protocol, and modified intention-to-treat eradication rates were (amoxicillin) 88.5% (138/156, 95% confidence interval (CI) 83.4-93.5%), 93.7% (133/142, 95% CI 89.7-97.7%), and 92.6% (138/149, 95% CI 88.4-96.8%). With tetracycline, they were 87.2% (136/156, 95% CI 81.9-92.4%), 95.3% (122/128, 95% CI 91.7-99.0%), and 90.7% (136/150, 95% CI 86.0-95.3%). Amoxicillin-, tetracycline-, and metronidazole-resistant rates were 8.3, 1.0, and 87.8%, respectively. Non-inferiority was confirmed (P<0.025). Metronidazole resistance did not affect the efficacy of either therapy. Compliance was greater and moderate and severe adverse events were less among those receiving amoxicillin than those receiving tetracycline. The novel bismuth-containing quadruple therapy with metronidazole and amoxicillin is an alternative to classical bismuth quadruple therapy for H. pylori rescue treatment as it provides similar eradication with superior safety and compliance.

Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables. As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups. The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance. ClinicalTrials.gov, ChiCTR 1900023646.

BackgroundBismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori.MethodsTreatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication.ResultsThe per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups.ConclusionCompared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).